A rat model of human immunodeficiency virus 1 encephalopathy using envelope glycoprotein gp120 expression delivered by SV40 vectors.
A rat model of human immunodeficiency virus 1 encephalopathy using envelope glycoprotein gp120 expression delivered by SV40 vectors.
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DOI：
10.1097/nen.0b013e3181a10f83
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发表时间：
2009-05
影响因子：
3.2
通讯作者：
Strayer DS
中科院分区：
文献类型：
--
作者：
Louboutin JP;Agrawal L;Reyes BA;Van Bockstaele EJ;Strayer DS
Human immunodeficiency virus (HIV)-1 encephalopathy (HIVE) is thought to result in part from the toxicity of HIV-1 envelope (Env) glycoprotein gp120 for neurons. Experimental systems for studying the effects of gp120 and other HIV proteins on the brain have been limited to the acute effects of recombinant proteins in vitro or in vivo or simian immunodeficiency virus-infected monkeys. We describe an experimental rodent model of ongoing gp120-induced neurotoxicity in which HIV-1 Env is expressed in the brain using a SV40-derived gene delivery vector, SV(gp120). When it is inoculated stereotaxically into the rat caudate putamen (CP), SV(gp120) caused a partly hemorrhagic lesion in which neuron and other cell apoptosis continue for at least 12 weeks. HIV gp120 is expressed throughout this time and some apoptotic cells are gp120-positive. Malonaldehyde and 4-hydroxynonenal assays indicated that there was lipid peroxidation in these lesions. Prior administration of recombinant SV40 vectors carrying antioxidant enzymes, Cu/Zn superoxide dismutase or glutathione peroxidase was protective from SV(gp120)-induced oxidative injury and apoptosis. Thus, in vivo inoculation of SV(gp120) into the rat CP causes ongoing oxidative stress and apoptosis in neurons and may therefore represent a useful animal model for studying the pathogenesis and treatment of HIV-1 Env-related brain damage.
